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Risk factors for central retinal artery occlusion in young patients

Published:December 05, 2020DOI:https://doi.org/10.1016/j.jcjo.2020.11.008
      The acute irreversible loss of vision associated with central retinal artery occlusion (CRAO) can be devastating, especially in young patients. The literature has revealed potential risk factors, including hypercoagulability, trauma, sickle cell disorders, cardiac valvular disease, carotid stenosis, use of oral contraceptives, pregnancy, collagen vascular disease, increased intraocular pressure, optic nerve drusen, congenital prepapillary arterial loop, intravenous drug abuse, migraine, vasculitis, and perioperative factors in young patients with CRAO.
      • Brown GC
      • Magargal LE
      • Shields JA
      • Goldberg RE
      • Walsh PN
      Retinal arterial obstruction in children and young adults.
      • Xia T
      • Zarbin MA
      • Bhagat N
      Retinal artery occlusion in young patients: a 6-year review.
      • Ratra D
      • Dhupper M.
      Retinal arterial occlusions in the young: systemic associations in Indian population.
      This retrospective case-control study aims to evaluate systemic and ocular comorbidities associated with CRAO in young patients.
      This study was performed using data from the 2002–2014 National Inpatient Sample (NIS) Database.
      HCUP Nationwide Inpatient Sample (NIS)
      Healthcare Cost and Utilization Project (HCUP).
      ,
      HCUP National Inpatient Sample (NIS)
      Healthcare Cost and Utilization Project (HCUP).
      Cases included 522 (weighted) hospitalized young adults between the ages of 20 and 45 years with an admitting diagnosis of acute CRAO, and controls, matched by age and sex, were 5430 (weighted) individuals who did not have any diagnosis of retinal artery occlusion. The average age of subjects in the CRAO and non-CRAO cohorts was 37.3 and 37.4 years, respectively (p = 0.800). Men constituted 58.4% and 56.6% of the non-CRAO and CRAO cohorts, respectively (p = 0.400). The ethnic background of the CRAO cases versus controls included White participants 42.1% versus 55.9% (p < 0.001), Black participants 28.1% versus 8.2% (p < 0.001), Hispanic participants 4.5% versus 25.6% (p < 0.001), Asian/Pacific Islander participants 4.7% versus 2.0% (p < 0.001), and Native American participants 0% versus 6.9% (p < 0.001).
      A higher prevalence of certain systemic comorbidities was noted in CRAO cases compared with controls (Table 1); these comorbidities included hypertension 41.4% versus 23.3%, tobacco use 32.3% versus 23.7%, hyperlipidemia 21.0 versus 9.2, cardiac valvular disease 9.6 versus 2.2, and migraine 6.7 versus 2.7. Carotid stenosis, history of cerebral stroke, sickle cell disease, atherosclerosis, and aortic disease/aneurysm were significantly more prevalent in CRAO cases. Acute thromboembolic events were reported during hospitalization of CRAO patients and included Deep Vein Thrombosis or Pulmonary Embolism (4.7%), ischemic stroke (4.0%), and Transient Ischemic Attack (1.1%). Furthermore, 9.6% of cases underwent cerebral angiography, and 29.1% echocardiography. No patients underwent endarterectomy, and no in-hospital deaths were reported. The length of hospitalization varied significantly between cases and controls (3.45 days vs 4.29 days; p < 0.001), and no significant difference was found in the hospital cost per day between the cases and controls ($9964 vs $9283; p = 0.083).
      Table 1Comparison of patients with and without CRAO
      VariableControls (n = 5430)Cases (n = 522)p
      Count%Count%
      Age
      Average age (y)37.3037.380.800
      Age group (y)0.566
      20–29105519.409618.40
      30–45437580.6042681.60
      Sex0.400
      Men317258.4029556.60
      Women225841.6022743.40
      Ethnicity
      White303355.9022042.10<0.001
      Black4448.2014728.10<0.001
      Hispanic139125.60244.50<0.001
      Asian/Pacific Islander1082.00254.70<0.001
      Native American3776.9000.00<0.001
      Other50.10303.90<0.001
      Systemic comorbidities
      Aortic dissection aneurysm50.10101.90<0.001
      Atherosclerosis320.60101.900.001
      Atrial fibrillation/flutter1152.1051.000.072
      Carotid dissection50.1000.000.488
      Carotid stenosis50.10305.80<0.001
      Cocaine use1011.9050.900.137
      Bleeding diathesis1993.70203.900.814
      Congestive heart failure891.60142.800.076
      DVT/PE (history)1572.90254.700.017
      Diabetes with chronic complications1623.00142.800.719
      Diabetes without chronic complications5299.70295.600.002
      Intravenous drug use1102.0050.900.094
      Hyperlipidemia5019.2010921.00<0.001
      Primary hypercoagulable state190.30254.90<0.001
      Hypertension126723.3021441.40<0.001
      Leukemia631.2000.000.013
      Non-Hodgkin lymphoma290.5000.000.094
      Migraine1492.70356.70<0.001
      Obesity4989.206011.500.072
      Pregnancy140.3000.000.245
      Pseudotumour cerebri100.2000.000.326
      Rheumatoid arthritis/collagen vascular diseases711.3040.900.299
      Sickle cell disease trait430.8091.800.029
      Stroke (history)430.80193.70<0.001
      Syphilis100.2091.80<0.001
      Systemic vasculitides00.0050.90<0.001
      Tobacco use128823.7016932.30<0.001
      Cardiac valve disease1202.20509.60<0.001
      Glaucoma with NVG40.10101.80<0.001
      In-hospital complications
      DVT/PE (acute)2113.90254.700.317
      Myocardial infarction (acute)430.8000.000.041
      Ischemic stroke50.10214.00<0.001
      Hemorrhagic stroke100.2000.000.326
      Transient ischemic attack190.4061.100.007
      Systemic venous thrombosis521.00132.500.001
      In-hospital procedures
      Cerebral angiography440.80509.60<0.001
      Carotid ultrasound00.00152.80<0.001
      Echocardiography480.9015229.10<0.001
      Medication
      Anticoagulation1222.30305.70<0.001
      Antiplatelet140.3000.000.245
      Aspirin591.1040.800.495
      Hospital course
      Mean length of stay (days)4.293.45<0.001
      Mean cost per day (dollars)928399640.083
      Died during hospitalization190.4000.000.176
      DVT = Deep Vein Thrombosis. PE = Pulmonary Embolism.
      Comorbidities that significantly increased the risk of CRAO included systemic vasculitides (Odds Ratio (OR) = 164.68), carotid stenosis (OR = 61.66), glaucoma (OR = 26.48), hypercoagulable state (OR = 14.82), syphilis (OR = 5.40), cardiac valve disease (OR = 3.36), migraine (OR = 3.14), and hypertension (OR = 1.97) (Table 2).
      Table 2Results of regression analysis
      VariableUnivariablepMultivariablep
      Bonferroni correction: p = 0.003.
      Age group (y)
      20–291.00Ref1.00Ref
      30–451.06 (0.84–1.34)0.597
      Sex
      Women1.00Ref
      Men1.08 (0.90–1.29)0.413
      Ethnicity
      White1.00Ref
      Black4.39 (3.54–5.44)<0.0013.56 (2.77–4.56)<0.001
      Hispanic0.14 (0.09–0.21)<0.0010.23 (0.15–0.36)<0.001
      Asian/Pacific Islander2.47 (1.58–3.86)<0.0012.86 (1.78–4.59)<0.001
      Native American0.01 (0.00–0.21)<0.0010.02 (0.00–0.35)0.007
      Other40.93 (15.55–107.71)<0.00150.67 (18.96–135.4)<0.001
      Systemic comorbidities
      Aortic dissection aneurysm19.92 (6.75–58.81)<0.0014.55 (1.07–19.41)0.041
      Atherosclerosis3.38 (1.65–6.91)<0.0013.06 (1.20–7.76)0.019
      Atrial fibrillation flutter0.49 (0.21–1.16)0.106
      Carotid dissection0.96 (0.04–23.12)0.980
      Carotid stenosis62.86 (24.76–159.61)<0.00161.66 (23.83–159.54)<0.001
      Bleeding diathesis1.10 (0.70–1.75)0.678
      Congestive heart failure1.76 (1.00–3.07)0.0481.19 (0.64–2.19)0.584
      DVT/PE (history)1.68 (1.09–2.59)0.0190.65 (0.36–1.17)0.147
      Diabetes with chronic complications0.96 (0.56–1.64)0.870
      Diabetes without chronic complications0.56 (0.38–0.82)0.0030.44 (0.29–0.69)<0.001
      Intravenous drug use0.47 (0.19–1.17)0.104
      Hyperlipidemia2.61 (2.08–3.29)<0.0011.37 (1.02–1.84)0.035
      Primary hypercoagulable state14.5 (7.94–26.47)<0.00114.82 (6.52–33.71)<0.001
      Hypertension2.32 (1.93–2.79)<0.0011.97 (1.58–2.46)<0.001
      Leukemia0.08 (0.00–1.34)0.079
      Non-Hodgkin lymphoma0.17 (0.01–2.97)0.227
      Migraine without cerebral infarction2.56 (1.75–3.74)<0.0013.14 (2.04–4.82)<0.001
      Obesity1.30 (0.97–1.72)0.075
      Peripheral artery disease2.97 (1.80–4.89)<0.0010.42 (0.18–0.99)0.048
      Pregnancy0.36 (0.02–6.59)0.488
      Pseudotumour cerebri0.50 (0.03–9.92)0.652
      Rheumatoid arthritis0.72 (0.29–1.82)0.492
      Sickle cell disease trait2.35 (1.16–4.75)0.0180.35 (0.13–0.97)0.044
      Stroke (history)4.87 (2.83–8.38)<0.0012.20 (1.11–4.34)0.024
      Syphilis10.24 (4.16–25.17)<0.0015.40 (1.89–15.45)0.002
      Systemic vasculitides108.98 (4.45–2666.38)0.04164.68 (5.60–4846.00)0.003
      Tobacco use1.54 (1.27–1.87)<0.0011.21 (0.97–1.52)0.088
      Cardiac valve disease4.73 (3.36–6.66)<0.0013.36 (2.19–5.16)<0.001
      Glaucoma (includes neovascular glaucoma)23.27 (7.35–73.66)<0.00126.48 (7.95–88.19)<0.001
      DVT = Deep Vein Thrombosis. PE = Pulmonary Embolism.
      low asterisk Bonferroni correction: p = 0.003.
      Recent evidence suggests that cerebrovascular accidents may occur within a month of acute CRAO in up to 25% of cases; the American Heart Association and American Academy of Ophthalmology recommend that, irrespective of age, all of these patients should undergo urgent stroke work-up.
      • Flaxel CJ
      • Adelman RA
      • Bailey ST
      • et al.
      Retinal and Ophthalmic Artery Occlusions Preferred Practice Pattern.
      This study showed that a myriad of systemic conditions and glaucoma are risk factors for acute CRAO in young adults.
      Because the present study uses a national database, it is retrospective in nature, and one cannot determine causality. Furthermore, the accuracy of the analysis depends on the accuracy of the health care providers coding the diagnoses. These limitations are not unique to this database or study. Additionally, although the control group was matched by sex and age, it was not matched by ethnicity, which may introduce variation; however, the variation is likely modest and unlikely to affect the regression analysis, which includes ethnicity. Lastly, because the cases and controls of this study are inpatients, there is likely to be a higher prevalence of chronic conditions requiring multiple hospitalizations than what would be seen in a study of outpatients.

      Footnotes and Disclosure

      Marco A. Zarbin reports personal fees from Genentech/Roche, Novartis Pharma AG, Iveric Bio, Perfuse Therapeutics, Selphagy/Life Biosciences, Frequency Therapeutics, and Chengdu Kanghong Biotech, and is cofounder of NVasc. The other authors have no financial disclosures.

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